This invention relates to novel prostanoic acid derivatives, processes for the production thereof, as well as novel intermediates formed during this process.
The novel prostanoic acid derivatives exhibit a pharmacological spectrum of activity similar to that of the natural prostaglandins and are useful for similar purposes.
Prostaglandins are C.sub.20 -unsaturated fatty acids showing a great variety of physiological effects (T. O. Oesterling et al., J. Pharmaceutical Sciences 61 [(1972] 1861-1895). Such effects are, for example, vasodilation, bronchodilatation, inhibition of gastric acid secretion, inhibition of blood platelet aggregation. Various natural prostaglandins, such as, for example prostaglandin E.sub.2 and prostaglandin F.sub.2.sub..alpha., are suitable for bringing about the onset of menstruation, for the induction of abortion, and for the induction of labor.
The conventional prostaglandins are derivatives of prostanoic acid having the following formula: ##STR4##
Examples of known prostaglandins, called PG hereinbelow, are: ##STR5##
PG E.sub.2, PG F.sub.2.sub..alpha., PG A.sub.2 correspond to the compounds of the PG'.sub.1 series with respect to their basic structure, except the linking of the number 5 and 6 carbon atoms is different. In the PG'.sub.2 series, the C-5 and C-6 carbon atoms are linked by a cis-double bond.
PG F.sub.2.sub..alpha. has the following formula: ##STR6##
PG E.sub.3, PG F.sub.3.sub..alpha., and PG A.sub.3 differ from the corresponding PG'.sub.2 compounds in that the C-17 and C-18 carbon atoms are linked by a cis-double bond.
PG F.sub.3.sub..alpha. has the formula: ##STR7##
It is generally known that the physiological activities of the prostaglandins in the mammal organism as well as in vitro are only of a brief duration, since these substances are rapidly converted into pharmacologically inactive metabolic products. Thus, a physiologically inactive metabolite is formed by oxidation of the allyl hydroxy function on the C-15 carbon atoms by the action of 15-hydroxyprostaglandin dehydrogenases. For example, from PG F.sub.2.sub..alpha. the ensuing 13,14-dihydro-15-dehydro derivative is formed by this oxidation as well as by a hydrogenating step, as the main metabolite (E. Granstrom and B. Samuelson, Eur.J.Biochem. 10 [1969], 411): ##STR8## which possesses the physiological activities typical for this class of substances only to a very weakened extent.
Therefore, it is desirable to provide prostaglandin analogs having a spectrum of effectiveness comparable to that of the natural prostaglandins, and to make structural changes whereby the duration and selectivity of effectiveness are increased.
It has now been found that 16-dioxy derivatives of the prostaglandins exhibit surprisingly good physiological activities. These novel prostaglandin analogs satisfy the above-mentioned requirement, i.e., they are superior in their effectiveness to the natural prostaglandins. Moreover, the effect lasts over a longer period of time.